Cellular/Molecular

Autaptic cultures, in which isolated cells form synapses with themselves, are often used to study synaptic function, but autapses do not necessarily act the same way as synapses between neurons. This is underscored by results reported by Liu et al. Because previous studies involving knock-out of synaptotagmin I—a protein required for calcium-triggered synaptic vesicle release—had yielded conflicting results, Liu et al. examined whether the effects differed in cultures containing different numbers of neurons. In cultures containing many neurons that all lacked synaptotagmin I, evoked neurotransmitter release was reduced, fewer synaptic vesicles were docked in the presynaptic terminal, and the probability of release following stimulation was reduced, but the probability of spontaneous release rose. In contrast, none of these synaptic properties were altered in autaptic cultures of isolated neurons lacking synaptotagmin I. The results also suggest that synaptotagmin I normally limits fusion of synaptic vesicles with the plasma membrane in the absence of calcium.

Tomographic reconstruction of a synapse in a wild-type neuron (top) or a neuron lacking synaptotagmin I (bottom) in cultures containing many neurons. Loss of synaptotagmin I reduces the number of vesicles. See the article by Liu et al. for details.

Development/Plasticity/Repair

Most cortical projection neurons derive from neural progenitor cells in the ventricular zone. During development, progenitors undergo several rounds of symmetric cell divisions, greatly increasing their number before asymmetric divisions produce daughter cells that differentiate into neurons and glia. The balance between progenitor proliferation and differentiation is a critical determinant of the number of neurons produced. Previous studies indicated that ephrin-B, a transmembrane protein involved in intercellular communication at several developmental stages, helps to maintain the progenitor state in the ventricular zone, possibly by interacting with the transcriptional repressor ZHX2. Wu et al. confirmed this interaction and showed that both proteins are expressed in the ventricular zone of developing mouse cortex. Analysis of progenitor cell and neuronal markers indicated that inhibiting ZHX2 function led to premature differentiation, whereas overexpression of ZHX2 increased the number of progenitors. Coexpression of the cytoplasmic domain of ephrin-B enhanced transcriptional repression by ZHX2 and thus helped to maintain progenitors.

Behavioral/Systems/Cognitive

Synaptic plasticity and learning have long been known to require protein synthesis. Recent studies have shown that the mammalian target of rapamycin (mTOR)—which regulates synthesis of a small subset of proteins by regulating translation initiation and elongation—is also required for several forms of plasticity. This week, Belelovsky et al. report that after mice experience a novel taste, mTOR is activated in two waves: at 15 and 180 min. Taste learning was demonstrated by the diminished ability of the taste to produce aversion in a subsequent conditioning experiment. This effect was reduced when rapamycin was injected into the gustatory cortex before or after the initial presentation of the novel taste, suggesting that both early and late waves of mTOR activation are required for novel taste learning. Injection of rapamycin into gustatory cortex also reduced expression of the postsynaptic density scaffolding protein PSD-95, a putative target of mTOR regulation.

Neurobiology of Disease

Laser-scanning photostimulation/glutamate uncaging (LSPS) is useful for mapping the laminar distribution of presynaptic partners of cortical neurons. Researchers using this technique usually restrict analysis to postsynaptic currents that occur >10 ms after the laser stimulus to exclude those resulting from direct activation of presynaptic terminals via kainate receptors. But Brill and Huguenard have found that LSPS/glutamate uncaging predominantly activates somal AMPA receptors. They now present evidence that fast-spiking interneurons (basket or chandelier cells) elicit IPSCs with latencies <10 ms in pyramidal cells and in other fast-spiking interneurons. These IPSCs were not blocked by kainate receptor antagonists, suggesting they were not generated via direct activation of the presynaptic terminal. Short-latency IPSCs were elicited only when stimulation occurred within 250 μm of the recorded soma, consistent with previous findings that fast-spiking interneurons usually target nearby neurons and synapse perisomatically on pyramidal cells. In contrast, longer-latency IPSCs could be elicited in pyramidal cells by more distal stimulation.